Amino thiol peptides

Abstract

Analgesic and hypotensive activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein R 1 and R 2 are each independently hydrogen, alkyl, carboxyalkyl, halo substituted alkyl, hydroxyalkyl, aminoalkyl, mercaptoalkyl, alkylthioalkyl, (cycloalkyl)alkyl, (heteroaryl)alkyl, arylalkyl, carbamoylalkyl, guanidinylalkyl, or heteroaryl; R 3 is hydroxy, alkoxy, (substituted alkyl)oxy, arylalkoxy, (heteroaryl)alkoxy, or --NY 1 Y 2 , wherein Y 1 and Y 2 are each independently hydrogen, alkyl, aryl, or arylalkyl, or Y 1 is hydrogen and Y 2 is substituted alkyl or (heteroaryl)alkyl; A 1 is glycyl, alanyl, leucyl, phenylalanyl, arginyl, sarcosyl, seryl, asparagyl, lysyl, glutamyl, histidyl, tryptophyl, cysteinyl, methionyl, threonyl, tyrosyl, leucyl, valyl, aspartyl, prolyl, norleucyl, norvalyl, or ##STR2## wherein n 6 is an integer of 2 to 15; A 2 , A 3 , A 4 and A 5 each is independently glycyl, alanyl, leucyl, phenylalanyl, arginyl, sarcosyl, seryl, asparagyl, lysyl, glutamyl, histidyl, tryptophyl, cysteinyl, methionyl, threonyl, tyrosyl, leucyl, valyl, aspartyl, prolyl, norleucyl, or norvalyl; and n 1 , n 2 , n 3 , n 4 and n 5 each is independently 0 or 1.

What is claimed is: 
     
       1. A compound having the formula ##STR37## and pharmaceutically acceptable salts thereof, wherein R 1  and R 2  are each independently hydrogen, alkyl, carboxyalkyl, halo substituted alkyl, hydroxyalkyl, aminoalkyl, mercaptoalkyl, alkylthioalkyl, (cycloalkyl)alkyl, (heteroaryl)alkyl, arylalkyl, carbamoylalkyl, guanidinylalkyl, or heteroaryl; R 3  is hydroxy, alkoxy, (substituted alkyl)oxy, arylalkoxy, (heteroaryl)alkoxy, or --NY 1  Y 2 , wherein Y 1  and Y 2  are each independently hydrogen, alkyl, aryl, or arylalkyl, or Y 1  is hydrogen and Y 2  is substituted alkyl or (heteroaryl)alkyl;   A 1  is glycyl, alanyl, leucyl, phenylalanyl, arginyl, sarcosyl, seryl, asparagyl, lysyl, glutamyl, histidyl, tryptophyl, cysteinyl, methionyl, threonyl, tyrosyl, leucyl, valyl, aspartyl, prolyl, norleucyl, norvalyl, or ##STR38##  wherein n 6  is an integer of 2 to 15; A 2 , A 3 , A 4  and A 5  each is independently glycyl, alanyl, leucyl, phenylalanyl, arginyl, sarcosyl, seryl, asparagyl, lysyl, glutamyl, histidyl, tryptophyl, cysteinyl, methionyl, threonyl, tyrosyl, leucyl, valyl, aspartyl, prolyl, norleucyl, or norvalyl; and   n 1 , n 2 , n 3 , n 4  and n 5  each is independently 0 or 1.   
     
     
       2. A compound in accordance with claim 1 wherein n 1  is 1 and n 2 , n 3 , n 4  and n 5  are each 0. 
     
     
       3. A compound in accordance with claim 1 wherein R 1  is phenylmethyl and R 2  is phenylmethyl. 
     
     
       4. A compound in accordance with claim 1 wherein R 3  is hydroxy. 
     
     
       5. A compound in accordance with claim 1 wherein R 1  is phenylmethyl, R 2  is phenylmethyl, n 1  is 1, n 2 , n 3 , n 4  and n 5  are each 0 and R 3  is hydroxy. 
     
     
       6. The compound in accordance with claim 1, N-[N-(3-amino-2-mercapto-4-phenylbutyl)-L-phenylalanyl]-L-leucine.